5-103136856-A-G

Variant names:

• chr5-103136856-A-G
• rs74429703
• NM_001276277.3:c.401+34A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001276277.3(PPIP5K2):​c.401+34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,477,420 control chromosomes in the GnomAD database, including 1,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (528 hom., cov: 32)
  • Exomes 𝑓: 0.017 (553 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

Genes affected

PPIP5K2 (HGNC:29035): (diphosphoinositol pentakisphosphate kinase 2) This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]

PPIP5K2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive 100

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-103136856-A-G is Benign according to our data. Variant chr5-103136856-A-G is described in ClinVar as Benign. ClinVar VariationId is 1261411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIP5K2	NM_001276277.3	MANE Select	c.401+34A>G		intron	N/A	NP_001263206.1	O43314-1
	PPIP5K2	NM_001281471.3		c.401+34A>G		intron	N/A	NP_001268400.1	A0A087WZV0
	PPIP5K2	NM_001345873.2		c.401+34A>G		intron	N/A	NP_001332802.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIP5K2	ENST00000358359.8	TSL:1 MANE Select	c.401+34A>G		intron	N/A	ENSP00000351126.3	O43314-1
	PPIP5K2	ENST00000414217.5	TSL:1	c.401+34A>G		intron	N/A	ENSP00000416016.1	O43314-2
	PPIP5K2	ENST00000613674.4	TSL:2	c.401+34A>G		intron	N/A	ENSP00000482907.1	A0A087WZV0

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7911 AN: 152184 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0397

GnomAD2 exomes AF: 0.0195 AC: 4883 AN: 250774 AF XY: 0.0163

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00885

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00286

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0166 AC: 22028 AN: 1325118 Hom.: 553 Cov.: 21 AF XY: 0.0155 AC XY: 10324 AN XY: 666722

African (AFR) AF: 0.166 AC: 5087 AN: 30614

American (AMR) AF: 0.0117 AC: 521 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00743 AC: 188 AN: 25310

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38962

South Asian (SAS) AF: 0.00120 AC: 100 AN: 83370

European-Finnish (FIN) AF: 0.00351 AC: 186 AN: 52998

Middle Eastern (MID) AF: 0.0127 AC: 70 AN: 5518

European-Non Finnish (NFE) AF: 0.0150 AC: 14799 AN: 987882

Other (OTH) AF: 0.0192 AC: 1076 AN: 55924

GnomAD4 genome AF: 0.0521 AC: 7936 AN: 152302 Hom.: 528 Cov.: 32 AF XY: 0.0495 AC XY: 3684 AN XY: 74490

African (AFR) AF: 0.160 AC: 6663 AN: 41558

American (AMR) AF: 0.0161 AC: 246 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0132 AC: 900 AN: 68012

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0288 Hom.: 38

Bravo AF: 0.0583

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs74429703; hg19: chr5-102472560;